卵巢癌独特型疫苗免疫接种方案的探讨  

Determination of optimal protocol for immunization with idiotypic vaccine of ovarian carcinoma.

作　　者：王建六[1] 钱和年[1] 冯捷[1] 崔恒[1] 李文锦[1] 傅天云[1] 韦平[1] 

机构地区：[1]北京医科大学第二临床医学院妇科肿瘤中心,100034

出　　处：《现代妇产科进展》1999年第3期220-225,共6页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金

摘　　要：目的：探讨卵巢癌抗独特型抗体（６Ｂ１１ ）疫苗免疫接种的理想方案。方法：用６Ｂ１１ 免疫ＢｃＦ１ 小鼠，观察基础免疫和加强免疫诱导的免疫应答情况，探讨加强免疫间隔时间、剂量及免疫途径对诱导免疫应答的影响，基础免疫为６Ｂ１１ １００μｇ—ＫＬＨ＋ ＣＦＡ，加强免疫为６Ｂ１１—ＫＬＨ＋ ＩＦＡ（或ＰＢＳ），免疫部位为小鼠尾根及足底皮下或腹腔。观察指标：体液免疫为免疫鼠血清中抗原特异结合性抗独特型抗体（Ａｂ３ ）滴度，细胞免疫为免疫鼠脾脏淋巴细胞ＣＤ４＋ 、ＣＤ８＋ 亚群的变化。结果：（１）６Ｂ１１ 基础免疫后，Ａｂ３ 阳性率为８０．００％ ，Ａｂ３ 滴度高峰在第１４～２１天（１：３２０），ＣＤ４＋ 亚群增加，ＣＤ＋８ 亚群变化不明显；（２）间隔４ 周加强免疫诱导的Ａｂ３ 滴度较２ 周者高，ＣＤ４＋ 亚群增加明显；６Ｂ１１５０μｇ 加强免疫诱导的免疫应答强于３０、１５μｇ；皮下途径加强免疫诱导的免疫应答略强于腹腔注射；（３）６Ｂ１１３ 次免疫后，Ａｂ３ 产生快（第３天１：３２０），滴度高（最高１：６４０），持续时间长（第４９天为１：４０），ＣＤ＋４ ／ＣＤ８＋ 比值明显增加。结论：卵巢癌抗独特型抗体６Ｂ１１可作为肿瘤疫苗诱导ＢｃＦ１小鼠?Objective:To determine the optimal protocol for immunization with anti idiotypic antibody(6B11)to be as ovarian tumor vaccine in BCF1 mice.Methods:6B11 was studied for the times of immunization,the dosage,the intervals,as well as the route of immunization.6B11 100μg coupling with KLH in complete Freund's adjuvant(CFA)was injected subcutaneously(s.c)on the tail root and the back side of foot pads as the basic immunization.After 2 and 4 weeks,6B11 50μg coupling with KLH in incomplete Freund's adjuvant(IFA) was injected at the same locations respectively.At the same time,the immune responses were compared in different dosages(50μg,30μg and 15μg),and different locations〔s.c and peritoneal cavity(i.p)〕.Ab3 which could specifically bind to the antigen was detected in the sera of immunized mice by ELISA.The CD + 4 and CD + 8 T cell were detected by flow cytometry.Results:(1)After basic immunization,the positive rate of Ab3 was 80.00%.CD + 4 T cell was increased,but no change of CD + 8 T cell noticed.(2)Immunization with 4 weeks interval induced more intense immune response than 2 weeks interval with higher titer of Ab3 and increased CD + 4 T cell,the immune response was weaker in the dosage of 15μg and 30μg than 50μg,no obvious difference was noticed between the s.c with IFA and i.p with PBS.(3)After 3 times immunization with 6B11,A63 could be induced rapidly(1:320 on the 3rd day)with the highest titer 1:640,and persisted longer(1:40 on 49th day),with increased CD + 4/CD + 8 ratio.Conclusions:The humoral and cellular immune responses can be induced in BcF 1 mice by the antiidiotypic antibody to ovarian carcinoma(6B 11 )as a tumor vaccine.The best protocol should be administered multi subcutaneously in a dose of 50 100ug 3 times with a interval of 3 weeks.

关 键 词：卵巢肿瘤 独特型抗体疫苗 免疫应答 免疫接种 

分 类 号：R737.310.1[医药卫生—肿瘤]